Carcinogenesis, Vol 18, 2299-2305, Copyright © 1997 by Oxford University Press
FL Martin, S Venitt, PL Carmichael, C Crofton-Sleigh, EM Stone, KJ Cole, BA Gusterson, PL Grover and DH Phillips
The presence of DNA damage in primary cultures of human mammary epithelial
cells (HMECs), and the ability of extracts of human mammary lipid to cause
such damage, has been investigated. Lipid extracts, prepared by a
solid-phase procedure, and HMECs were obtained from breast tissue removed
from healthy women (ages 18-50 years) who were resident in the UK and
undergoing elective reduction mammoplasties. DNA single strand breaks
(SSBs) were detected using the single-cell gel assay (comet assay) with
alkaline electrophoresis (pH 12.3) and quantified by measuring comet tail
length (CTL) (microm). Untreated HMECs and HMECs incubated (30 min, 37
degrees C) with a mammary lipid extract, with or without DNA-repair
inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C), were
examined. Ionizing radiation was used as a positive control. An active
lipid extract gave a linear dose- response over the range 2.0-12.2 g
equivalents. When MCL-5 cells, a line of metabolically-competent human
lymphoblastoid cells, were used to compare the DNA-damaging properties of
lipid extracts from six different donors, significant interindividual
variations (median CTLs were 15.0, 53.5, 32.5, <4.0, <4.0 and 77.5
microm respectively) were observed. In eight subjects, the donors' HMECs
were examined both before and after treatment with extracts of that donor's
own lipid. Pre- existing DNA damage was detected in untreated HMECs from
some donors (median CTLs 22.0-37.5 microm) that was not present in others
(median CTLs 4.0-11.5 microm), and increases in CTL could be induced by
incubation with the matching lipid extract (8 g equivalent) in more than
half (five out of eight) the subjects examined (median CTL up to 111.0
microm). There was a tendency for the most active lipid extracts to be
those obtained from donors whose HMECs also contained the most pre-existing
DNA SSBs. The results of this pilot study may prove to be significant in
relation to the initiation of breast cancer.
ARTICLES
DNA damage in breast epithelial cells: detection by the single-cell gel (comet) assay and induction by human mammary lipid extracts
Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK.
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